Toxins

11 pages, 1403 KiB

Open AccessEditor’s ChoiceArticle

Evidence for Naturally Produced Beauvericins Containing N-Methyl-Tyrosine in Hypocreales Fungi

by Monika Urbaniak, Łukasz Stępień and Silvio Uhlig

Toxins 2019, 11(3), 182; https://doi.org/10.3390/toxins11030182 - 26 Mar 2019

Cited by 17 | Viewed by 4694

Beauvericin is a depsipeptide mycotoxin. The production of several beauvericin analogues has previously been shown among various genera among Hypocreales fungi. This includes so-called beauvenniatins, in which one or more N-methyl-phenylalanine residues is exchanged with other amino acids. In addition, a range [...] Read more.

Beauvericin is a depsipeptide mycotoxin. The production of several beauvericin analogues has previously been shown among various genera among Hypocreales fungi. This includes so-called beauvenniatins, in which one or more N-methyl-phenylalanine residues is exchanged with other amino acids. In addition, a range of “unnatural” beauvericins has been prepared by a precursor addition to growth medium. Our aim was to get insight into the natural production of beauvericin analogues among different Hypocreales fungi, such as Fusarium and Isaria spp. In addition to beauvericin, we tentatively identified six earlier described analogues in the extracts; these were beauvericin A and/or its structural isomer beauvericin F, beauvericin C, beauvericin J, beauvericin D, and beauvenniatin A. Other analogues contained at least one additional oxygen atom. We show that the additional oxygen atom(s) were due to the presence of one to three N-methyl-tyrosine moieties in the depsipeptide molecules by using different liquid chromatography–mass spectrometry-based approaches. In addition, we also tentatively identified a beauvenniatin that contained N-methyl-leucine, which we named beauvenniatin L. This compound has not been reported before. Our data show that N-methyl-tyrosine containing beauvericins may be among the major naturally produced analogues in certain fungal strains. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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10 pages, 431 KiB

Open AccessEditor’s ChoiceShort Communication

Reduction of Mycotoxins during Fermentation of Whole Grain Sorghum to Whole Grain Ting (a Southern African Food)

by Oluwafemi Ayodeji Adebo, Eugenie Kayitesi and Patrick Berka Njobeh

Toxins 2019, 11(3), 180; https://doi.org/10.3390/toxins11030180 - 25 Mar 2019

Cited by 51 | Viewed by 4967

Abstract

Mycotoxins are fungal secondary metabolites that pose health risks to exposed individuals, requiring necessary measures to reduce them. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), mycotoxins were quantified in whole grain sorghum and ting subsequently derived from two sorghum varieties (high and low tannin). [...] Read more.

Mycotoxins are fungal secondary metabolites that pose health risks to exposed individuals, requiring necessary measures to reduce them. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), mycotoxins were quantified in whole grain sorghum and ting subsequently derived from two sorghum varieties (high and low tannin). The whole grain (WG) ting samples were obtained by fermenting sorghum with Lactobacillus fermentum strains (FUA 3165 and FUA 3321). Naturally (spontaneously) fermented WG-ting under the same conditions were equally analysed. Among the mycotoxins investigated, fumonisin B₁ (FB₁), B₂ (FB₂), B₃ (FB₃), T-2 toxin (T-2), zearalenone (ZEA), alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL) were detected in sorghum. Results obtained showed that mycotoxin concentrations significantly (p ≤ 0.05) reduced after fermentation. In particular, L. fermentum FUA 3321 showed the capability to significantly (p ≤ 0.05) reduce all the mycotoxins by 98% for FB₁, 84% for T-2 and up to 82% for α-ZOL, compared to raw low tannin sorghum. Fermenting with the L. fermentum strains showed potential to effectively reduce mycotoxin contamination in whole grain ting. Thus, we recommended L. fermentum FUA 3321 in particular to be used as a potential starter culture in sorghum fermentation. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 2045 KiB

Open AccessEditor’s ChoiceArticle

Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis

by Samuel K. Kwofie, Bismark Dankwa, Kweku S. Enninful, Courage Adobor, Emmanuel Broni, Alfred Ntiamoah and Michael D. Wilson

Toxins 2019, 11(3), 181; https://doi.org/10.3390/toxins11030181 - 25 Mar 2019

Cited by 34 | Viewed by 7181

Abstract

Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin [...] Read more.

Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Wound healing processes involve activation of the blood platelets to release the contents of the dense granules mainly serotonin, calcium ions, and ADP/ATP by exocytosis into the bloodstream. The serotonin release results in attracting more platelets and mast cells to the wound site, with the mast cells also undergoing degranulation, releasing compounds into the bloodstream by exocytosis. Recent work has identified interference in the co-translational translocation of many secreted proteins via the endoplasmic reticulum and cell death involving Wiskott-Aldrich syndrome protein (WASP), Sec61, and angiotensin II receptors (AT2R). We hypothesized that mycolactone by being lipophilic, passively crosses cell membranes and binds to key proteins that are involved in exocytosis by platelets and mast cells, thus inhibiting the initiation of wound healing processes. Based on this, molecular docking studies were performed with mycolactone against key soluble n-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and regulators, namely Vesicle-associated membrane protein (VAMP8), Synaptosomal-associated protein (SNAP23, syntaxin 11, Munc13-4 (its isoform Munc13-1 was used), and Munc18b; and also against known mycolactone targets (Sec61, AT2R, and WASP). Munc18b was shown to be a plausible mycolactone target after the molecular docking studies with binding affinity of −8.5 kcal/mol. Structural studies and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding energy calculations of the mycolactone and Munc18b complex was done with 100 ns molecular dynamics simulations using GROMACS. Mycolactone binds strongly to Munc18b with an average binding energy of −247.571 ± 37.471 kJ/mol, and its presence elicits changes in the structural conformation of the protein. Analysis of the binding interactions also shows that mycolactone interacts with Arg405, which is an important residue of Munc18b, whose mutation could result in impaired granule exocytosis. These findings consolidate the possibility that Munc18b could be a target of mycolactone. The implication of the interaction can be experimentally evaluated to further understand its role in granule exocytosis impairment in Buruli ulcer. Full article

(This article belongs to the Special Issue Mycolactone: Lipid-Like Immunosuppressive Toxin of Buruli Ulcer)

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21 pages, 565 KiB

Open AccessEditor’s ChoiceReview

Harmful Effects and Control Strategies of Aflatoxin B₁ Produced by Aspergillus flavus and Aspergillus parasiticus Strains on Poultry: Review

by Ahmed Mohamed Fouad, Dong Ruan, HebatAllah Kasem El-Senousey, Wei Chen, Shouqun Jiang and Chuntian Zheng

Toxins 2019, 11(3), 176; https://doi.org/10.3390/toxins11030176 - 23 Mar 2019

Cited by 162 | Viewed by 10750

Abstract

The presence of aflatoxin B₁ (AFB₁) in poultry diets decreases the hatchability, hatchling weight, growth rate, meat and egg production, meat and egg quality, vaccination efficiency, as well as impairing the feed conversion ratio and increasing the susceptibility of birds [...] Read more.

The presence of aflatoxin B₁ (AFB₁) in poultry diets decreases the hatchability, hatchling weight, growth rate, meat and egg production, meat and egg quality, vaccination efficiency, as well as impairing the feed conversion ratio and increasing the susceptibility of birds to disease and mortality. AFB₁ is transferred from poultry feed to eggs, meat, and other edible parts, representing a threat to the health of consumers because AFB₁ is carcinogenic and implicated in human liver cancer. This review considers how AFB₁ produced by Aspergillus flavus and Aspergillus parasiticus strains can affect the immune system, antioxidant defense system, digestive system, and reproductive system in poultry, as well as its effects on productivity and reproductive performance. Nutritional factors can offset the effects of AFB₁ in poultry and, thus, it is necessary to identify and select suitable additives to address the problems caused by AFB₁ in poultry. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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19 pages, 640 KiB

Open AccessEditor’s ChoiceReview

Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock

by Teresa Krakauer

Toxins 2019, 11(3), 178; https://doi.org/10.3390/toxins11030178 - 23 Mar 2019

Cited by 88 | Viewed by 10206

Abstract

Staphylococcal enterotoxin B (SEB) and related superantigenic toxins produced by Staphylococcus aureus are potent activators of the immune system. These protein toxins bind to major histocompatibility complex (MHC) class II molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the activation [...] Read more.

Staphylococcal enterotoxin B (SEB) and related superantigenic toxins produced by Staphylococcus aureus are potent activators of the immune system. These protein toxins bind to major histocompatibility complex (MHC) class II molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the activation of both monocytes/macrophages and T lymphocytes. The bridging of TCRs with MHC class II molecules by superantigens triggers an early “cytokine storm” and massive polyclonal T-cell proliferation. Proinflammatory cytokines, tumor necrosis factor α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), and macrophage chemoattractant protein 1 elicit fever, inflammation, multiple organ injury, hypotension, and lethal shock. Upon MHC/TCR ligation, superantigens induce signaling pathways, including mitogen-activated protein kinase cascades and cytokine receptor signaling, which results in NFκB activation and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. In addition, gene profiling studies have revealed the essential roles of innate antimicrobial defense genes in the pathogenesis of SEB. The genes expressed in a murine model of SEB-induced shock include intracellular DNA/RNA sensors, apoptosis/DNA damage-related molecules, endoplasmic reticulum/mitochondrial stress responses, immunoproteasome components, and IFN-stimulated genes. This review focuses on the signaling pathways induced by superantigens that lead to the activation of inflammation and damage response genes. The induction of these damage response genes provides evidence that SEB induces danger signals in host cells, resulting in multiorgan injury and toxic shock. Therapeutics targeting both host inflammatory and cell death pathways can potentially mitigate the toxic effects of staphylococcal superantigens. Full article

(This article belongs to the Special Issue Toxins and Immunology)

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13 pages, 4878 KiB

Open AccessEditor’s ChoiceArticle

The Spodoptera exigua ABCC2 Acts as a Cry1A Receptor Independently of its Nucleotide Binding Domain II

by Daniel Pinos, María Martínez-Solís, Salvador Herrero, Juan Ferré and Patricia Hernández-Martínez

Toxins 2019, 11(3), 172; https://doi.org/10.3390/toxins11030172 - 22 Mar 2019

Cited by 18 | Viewed by 5212

Abstract

ABC proteins are primary-active transporters that require the binding and hydrolysis of ATP to transport substrates across the membrane. Since the first report of an ABCC2 transporter as receptor of Cry1A toxins, the number of ABC transporters known to be involved in the [...] Read more.

ABC proteins are primary-active transporters that require the binding and hydrolysis of ATP to transport substrates across the membrane. Since the first report of an ABCC2 transporter as receptor of Cry1A toxins, the number of ABC transporters known to be involved in the mode of action of Cry toxins has increased. In Spodoptera exigua, a mutation in the SeABCC2 gene is described as genetically linked to resistance to the Bt-product Xentari^TM. This mutation affects an intracellular domain involved in ATP binding, but not the extracellular loops. We analyzed whether this mutation affects the role of the SeABCC2 as a functional receptor to Cry1A toxins. The results show that Sf21 cells expressing the truncated form of the transporter were susceptible to Cry1A toxins. Moreover, specific Cry1Ac binding was observed in those cells expressing the truncated SeABCC2. Additionally, no differences in the irreversible Cry1Ac binding component (associated with the toxin insertion into the membrane) were observed when tested in Sf21 cells expressing either the full-length or the truncated form of the SeABCC2 transporter. Therefore, our results point out that the partial lack of the nucleotide binding domain II in the truncated transporter does not affect its functionality as a Cry1A receptor. Full article

(This article belongs to the Special Issue Insecticidal Toxins from Bacillus thuringiensis)

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20 pages, 741 KiB

Open AccessEditor’s ChoiceReview

FGF23, Biomarker or Target?

by Cristian Rodelo-Haad, Rafael Santamaria, Juan R. Muñoz-Castañeda, M. Victoria Pendón-Ruiz de Mier, Alejandro Martin-Malo and Mariano Rodriguez

Toxins 2019, 11(3), 175; https://doi.org/10.3390/toxins11030175 - 22 Mar 2019

Cited by 47 | Viewed by 11455

Abstract

Fibroblast growth factor 23 (FGF23) plays a key role in the complex network between the bones and other organs. Initially, it was thought that FGF23 exclusively regulated phosphate and vitamin D metabolism; however, recent research has demonstrated that an excess of FGF23 has [...] Read more.

Fibroblast growth factor 23 (FGF23) plays a key role in the complex network between the bones and other organs. Initially, it was thought that FGF23 exclusively regulated phosphate and vitamin D metabolism; however, recent research has demonstrated that an excess of FGF23 has other effects that may be detrimental in some cases. The understanding of the signaling pathways through which FGF23 acts in different organs is crucial to develop strategies aiming to prevent the negative effects associated with high FGF23 levels. FGF23 has been described to have effects on the heart, promoting left ventricular hypertrophy (LVH); the liver, leading to production of inflammatory cytokines; the bones, inhibiting mineralization; and the bone marrow, by reducing the production of erythropoietin (EPO). The identification of FGF23 receptors will play a remarkable role in future research since its selective blockade might reduce the adverse effects of FGF23. Patients with chronic kidney disease (CKD) have very high levels of FGF23 and may be the population suffering from the most adverse FGF23-related effects. The general population, as well as kidney transplant recipients, may also be affected by high FGF23. Whether the association between FGF23 and clinical events is causal or casual remains controversial. The hypothesis that FGF23 could be considered a therapeutic target is gaining relevance and may become a promising field of investigation in the future. Full article

(This article belongs to the Special Issue Disposition of Uremic Toxins: The Challenges in Uremia)

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37 pages, 7260 KiB

Open AccessEditor’s ChoiceArticle

The Dual Prey-Inactivation Strategy of Spiders—In-Depth Venomic Analysis of Cupiennius salei

by Lucia Kuhn-Nentwig, Nicolas Langenegger, Manfred Heller, Dominique Koua and Wolfgang Nentwig

Toxins 2019, 11(3), 167; https://doi.org/10.3390/toxins11030167 - 19 Mar 2019

Cited by 37 | Viewed by 10581

Abstract

Most knowledge of spider venom concerns neurotoxins acting on ion channels, whereas proteins and their significance for the envenomation process are neglected. The here presented comprehensive analysis of the venom gland transcriptome and proteome of Cupiennius salei focusses on proteins and cysteine-containing peptides [...] Read more.

Most knowledge of spider venom concerns neurotoxins acting on ion channels, whereas proteins and their significance for the envenomation process are neglected. The here presented comprehensive analysis of the venom gland transcriptome and proteome of Cupiennius salei focusses on proteins and cysteine-containing peptides and offers new insight into the structure and function of spider venom, here described as the dual prey-inactivation strategy. After venom injection, many enzymes and proteins, dominated by α-amylase, angiotensin-converting enzyme, and cysteine-rich secretory proteins, interact with main metabolic pathways, leading to a major disturbance of the cellular homeostasis. Hyaluronidase and cytolytic peptides destroy tissue and membranes, thus supporting the spread of other venom compounds. We detected 81 transcripts of neurotoxins from 13 peptide families, whereof two families comprise 93.7% of all cysteine-containing peptides. This raises the question of the importance of the other low-expressed peptide families. The identification of a venom gland-specific defensin-like peptide and an aga-toxin-like peptide in the hemocytes offers an important clue on the recruitment and neofunctionalization of body proteins and peptides as the origin of toxins. Full article

(This article belongs to the Section Animal Venoms)

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30 pages, 4336 KiB

Open AccessEditor’s ChoiceArticle

Multi LC-MS/MS and LC-HRMS Methods for Determination of 24 Mycotoxins including Major Phase I and II Biomarker Metabolites in Biological Matrices from Pigs and Broiler Chickens

by Marianne Lauwers, Siegrid De Baere, Ben Letor, Michael Rychlik, Siska Croubels and Mathias Devreese

Toxins 2019, 11(3), 171; https://doi.org/10.3390/toxins11030171 - 19 Mar 2019

Cited by 62 | Viewed by 7515

Abstract

A reliable and practical multi-method was developed for the quantification of mycotoxins in plasma, urine, and feces of pigs, and plasma and excreta of broiler chickens using liquid chromatography–tandem mass spectrometry. The targeted mycotoxins belong to the regulated groups, i.e., aflatoxins, ochratoxin A [...] Read more.

A reliable and practical multi-method was developed for the quantification of mycotoxins in plasma, urine, and feces of pigs, and plasma and excreta of broiler chickens using liquid chromatography–tandem mass spectrometry. The targeted mycotoxins belong to the regulated groups, i.e., aflatoxins, ochratoxin A and Fusarium mycotoxins, and to two groups of emerging mycotoxins, i.e., Alternaria mycotoxins and enniatins. In addition, the developed method was transferred to a LC-high resolution mass spectrometry instrument to qualitatively determine phase I and II metabolites, for which analytical standards are not always commercially available. Sample preparation of plasma was simple and generic and was accomplished by precipitation of proteins alone (pig) or in combination with removal of phospholipids (chicken). A more intensive sample clean-up of the other matrices was needed and consisted of a pH-dependent liquid–liquid extraction (LLE) using ethyl acetate (pig urine), methanol/ethyl acetate/formic acid (75/24/1, v/v/v) (pig feces) or acetonitrile (chicken excreta). For the extraction of pig feces, additionally a combination of LLE using acetone and filtration of the supernatant on a HybridSPE-phospholipid cartridge was applied. The LC-MS/MS method was in-house validated according to guidelines defined by the European and international community. Finally, the multi-methods were successfully applied in a specific toxicokinetic study and a screening study to monitor the exposure of individual animals. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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16 pages, 1814 KiB

Open AccessEditor’s ChoiceArticle

Development of Sensitive and Reliable UPLC-MS/MS Methods for Food Analysis of Emerging Mycotoxins in China Total Diet Study

by Danlei Sun, Nannan Qiu, Shuang Zhou, Bing Lyu, Shuo Zhang, Jingguang Li, Yunfeng Zhao and Yongning Wu

Toxins 2019, 11(3), 166; https://doi.org/10.3390/toxins11030166 - 17 Mar 2019

Cited by 24 | Viewed by 4852

Abstract

With the climatic changes that have taken place during the last decade, the spectrum of fungal pathogens as well as mycotoxins has considerably changed. As a result, some emerging mycotoxins have been shown to occur frequently in agricultural products. In this study, a [...] Read more.

With the climatic changes that have taken place during the last decade, the spectrum of fungal pathogens as well as mycotoxins has considerably changed. As a result, some emerging mycotoxins have been shown to occur frequently in agricultural products. In this study, a sensitive and reliable method for the determination of 10 emerging mycotoxins (beauvericin, enniatin A, enniatin A1, enniatin B, enniatin B1, alternariol, alternariol monomethyl ether, altenuene, tentoxin, and tenuazonic acid) in 12 different food matrices (cereals, legumes, potatoes, meats, eggs, aquatic foods, dairy products, vegetables, fruits, sugars, beverages, and alcohol beverages) was developed and validated. After a simple extraction, a one-step sample clean-up by a HLB solid phase extraction (SPE) column was sufficient for all 12 food matrices prior to analysis with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Isotope internal standards ¹³C-TeA, TEN-d₃, and ¹³C-AFB2 were used for accurate quantification. Validation in terms of linearity, selectivity, sensitivity, accuracy, and precision (intra and inter-day variability) were evaluated for the 10 mycotoxins in all selected matrices. The sensitivity varied from 0.0004 to 0.3 ng mL⁻¹ (limits of detection) and from 0.002 to 0.9 ng mL⁻¹ (limits of quantitation). The recoveries of 10 mycotoxins in fortified samples were from 60.6% to 164% including very low spiking levels in all 12 food matrices, with relative standard deviations (RSDs) less than 12%. The proposed methodology was applied to the analysis of 60 samples collected from five provinces within the 6^th China Total Diet Study with the results discussed in detail. The advantages of sensitivity, accuracy, and robustness made it a powerful tool for emerging mycotoxin monitoring and dietary exposure assessment. Full article

(This article belongs to the Special Issue 2^nd MycoKey International Conference - Integrated Solutions for Mycotoxin Management)

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18 pages, 305 KiB

Open AccessEditor’s ChoiceArticle

Variation of Fungal Metabolites in Sorghum Malts Used to Prepare Namibian Traditional Fermented Beverages Omalodu and Otombo

by Sylvia N. Nafuka, Jane M. Misihairabgwi, Ronnie Bock, Anthony Ishola, Michael Sulyok and Rudolf Krska

Toxins 2019, 11(3), 165; https://doi.org/10.3390/toxins11030165 - 16 Mar 2019

Cited by 19 | Viewed by 4506

Abstract

Sorghum malts, which are important ingredients in traditional fermented beverages, are commonly infected by mycotoxigenic fungi and mycotoxins may transfer into the beverages, risking consumers’ health. Liquid chromatography–tandem mass spectrometry was used to determine variation of fungal metabolites in 81 sorghum malts processed [...] Read more.

Sorghum malts, which are important ingredients in traditional fermented beverages, are commonly infected by mycotoxigenic fungi and mycotoxins may transfer into the beverages, risking consumers’ health. Liquid chromatography–tandem mass spectrometry was used to determine variation of fungal metabolites in 81 sorghum malts processed for brewing of Namibian beverages, otombo (n = 45) and omalodu (n = 36). Co-occurrence of European Union (EU)-regulated mycotoxins, such as patulin, aflatoxins (B₁, B₂, and G₂), and fumonisins (B₁, B₂, and B₃) was detected in both malts with a prevalence range of 2–84%. Aflatoxin B₁ was quantified in omalodu (44%) and otombo malts (14%), with 20% of omalodu malts and 40% of otombo malts having levels above the EU allowable limit. Fumonisin B₁ was quantified in both omalodu (84%) and otombo (42%) malts. Emerging mycotoxins, aflatoxin precursors, and ergot alkaloids were quantified in both malts. Notably, 102 metabolites were quantified in both malts, with 96% in omalodu malts and 93% in otombo malts. An average of 48 metabolites were quantified in otombo malts while an average of 67 metabolites were quantified in omalodu malts. The study accentuates the need to monitor mycotoxins in sorghum malts intended for brewing and to determine their fate in the beverages. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

17 pages, 1286 KiB

Open AccessEditor’s ChoiceArticle

Study on Trichothecene and Zearalenone Presence in Romanian Wheat Relative to Weather Conditions

by Oana Stanciu, Cristina Juan, Houda Berrada, Doina Miere, Felicia Loghin and Jordi Mañes

Toxins 2019, 11(3), 163; https://doi.org/10.3390/toxins11030163 - 15 Mar 2019

Cited by 38 | Viewed by 4579

Abstract

To evaluate the influence of weather conditions on mycotoxin presence in wheat, deoxynivalenol (DON), 3-acetyldeoxynivalenol (3AcDON), 15-acetyldeoxynivalenol (15AcDON), fusarenon-X (FUS-X), nivalenol (NIV), HT-2 toxin (HT-2), T-2 toxin (T-2), diacetoxyscirpenol (DAS), neosolaniol (NEO) and zearalenone (ZEN) were evaluated in 102 Romanian wheat samples coming [...] Read more.

To evaluate the influence of weather conditions on mycotoxin presence in wheat, deoxynivalenol (DON), 3-acetyldeoxynivalenol (3AcDON), 15-acetyldeoxynivalenol (15AcDON), fusarenon-X (FUS-X), nivalenol (NIV), HT-2 toxin (HT-2), T-2 toxin (T-2), diacetoxyscirpenol (DAS), neosolaniol (NEO) and zearalenone (ZEN) were evaluated in 102 Romanian wheat samples coming from five wheat growing areas during 2015. Only six mycotoxins were detected, while FUS-X, DAS, NEO and NIV were not present in the wheat samples. Mycotoxin concentrations were correlated with precipitation and temperature values during anthesis and the preharvest period. Overall, the highest frequency was registered for DON, while the lowest frequency was registered for NIV. In the North Muntenia, DON and ZEN registered high frequencies (68% and 16%, respectively). This region was characterized in June and July by medium to high values of rainfall (41–100 mm/month) and normal temperatures (mean of 20.0 °C in June and 24.0 °C in July), suggesting that precipitation levels influence fungi and mycotoxin development to a greater extent compared to the influence of temperature. Full article

(This article belongs to the Collection Understanding Mycotoxin Occurrence in Food and Feed Chains)

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8 pages, 1724 KiB

Open AccessEditor’s ChoiceArticle

Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells

by Lv Chen, Shu Yang, Cong Wen, Shuilin Zheng, Yue Yang, Xiangling Feng, Jihua Chen, Dan Luo, Ran Liu and Fei Yang

Toxins 2019, 11(3), 164; https://doi.org/10.3390/toxins11030164 - 15 Mar 2019

Cited by 27 | Viewed by 3875

Abstract

Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in [...] Read more.

Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in hepatotoxicity induced by MC-LR remained unclear. The study aimed to investigate the impacts of miR-451a in HL7702 cells following treatment with 5 or 10 μM MC-LR. The comet assay indicated that MC-LR can influence Olive tail moment (OTM) in HL7702 cells. Furthermore, increase of miR-451a significantly repressed DNA damage and the protein expression level of γ-H2AX induced by MC-LR. Moreover, over-expression of miR-451a inhibited the expression level of p-AKT1 protein in cells following treatment by MC-LR. These results showed that miR-451a may protect from MC-LR-induced DNA damage by down-regulating the expression of p-AKT1, which provides new clues for the diagnosis and therapy policies for liver damage induced by MC-LR. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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9 pages, 403 KiB

Open AccessEditor’s ChoiceArticle

Natural Occurrence and Co-Contamination of Twelve Mycotoxins in Industry-Submitted Cool-Season Cereal Grains Grown under a Low Heat Unit Climate Condition

by Haitao Shi, Warren Schwab and Peiqiang Yu

Toxins 2019, 11(3), 160; https://doi.org/10.3390/toxins11030160 - 13 Mar 2019

Cited by 29 | Viewed by 4063

Abstract

This study aims to evaluate the prevalence of mycotoxins in industry-submitted cool-season barley and wheat grown under low heat unit climate conditions. Seventy-two barley samples and 83 wheat samples were submitted by producers and industry from May 2016 to May 2017. The concentrations [...] Read more.

This study aims to evaluate the prevalence of mycotoxins in industry-submitted cool-season barley and wheat grown under low heat unit climate conditions. Seventy-two barley samples and 83 wheat samples were submitted by producers and industry from May 2016 to May 2017. The concentrations of twelve common mycotoxins, including nivalenol (NIV), deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), ochratoxin A (OTA), zearalenone (ZEN), α-zearalenol (α-ZAL), β-zearalenol (β-ZAL), diacetoxyscirpenol (DAS), T-2 toxin (T-2), HT-2 toxin (HT-2), and aflatoxin B1 (AFB1), were determined using the liquid chromatography/tandem mass spectrometry method. Mycotoxins were detected in 40 barley (56%) and 35 wheat (42%) samples submitted by producers and industry. DON showed the highest incidence in barley (44%) and wheat (33%). None of the barley samples contained detectable DAS and no wheat samples tested positive for α-ZAL, DAS, T-2, or AFB1. Co-occurrence of DON and other mycotoxins was frequently observed. Among the mycotoxin-positive samples, 70% of barley samples and 54% of wheat samples were co-contaminated with at least two mycotoxins. Four barley (6%) and five wheat (6%) samples contained levels of DON above 1000 μg/kg (regulatory level in diets for lactating dairy animals) and HT-2 content in five barley (7%) and four wheat (5%) samples exceeded 100 μg/kg (regulatory level in diets for cattle and poultry). Overall, contamination of these mycotoxins was more frequent and more severe in barley in comparison with wheat that was submitted by producers and industry. Comprehensive strategies, including the prevention of Fusarium toxins contamination, the routine monitoring of their prevalence, the detoxification of them in feed and food, as well as the inhibition of their absorption in the gastrointestinal tract, are highly required. A rapid detection method needs to be developed to screen mycotoxins in industry-submitted cool-season cereal grains. Full article

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10 pages, 600 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Bacillus subtilis ANSB060 Biodegradation Product for the Reduction of the Milk Aflatoxin M₁ Content of Dairy Cows Exposed to Aflatoxin B₁

by Yongpeng Guo, Yong Zhang, Chen Wei, Qiugang Ma, Cheng Ji, Jianyun Zhang and Lihong Zhao

Toxins 2019, 11(3), 161; https://doi.org/10.3390/toxins11030161 - 13 Mar 2019

Cited by 20 | Viewed by 3932

Abstract

This study was conducted to determine the effect of Bacillus subtilis ANSB060 biodegradation product (BDP) in reducing the milk aflatoxin M₁ (AFM₁) content of dairy cows fed a diet contaminated with aflatoxin B₁ (AFB₁). Twenty-four Chinese Holstein [...] Read more.

This study was conducted to determine the effect of Bacillus subtilis ANSB060 biodegradation product (BDP) in reducing the milk aflatoxin M₁ (AFM₁) content of dairy cows fed a diet contaminated with aflatoxin B₁ (AFB₁). Twenty-four Chinese Holstein cows (254 ± 19 d in milk; milk production 19.0 ± 1.2 kg d⁻¹) were assigned to three dietary treatments, as follows: (1) control diet (CON), consisting of a basal total mixed ration (TMR); (2) aflatoxin diet (AF), containing CON plus 63 μg of AFB₁ kg⁻¹ of diet dry matter; and (3) aflatoxin diet plus BDP (AF + BDP), containing AF plus BDP at 0.2% of diet dry matter. The experiment lasted 12 days, including an AFB₁-dosing period from days one to eight, followed by a clearance period from days nine to twelve. Milk samples were collected on days 2, 4, 6, and 8–12, and the plasma was sampled on day 9, before morning feeding. Short-term AFB₁ exposure did not affect the milk production and composition. The plasma biochemical indices, except for lactic dehydrogenase (LDH), were also not changed by the AFB₁ intake. The plasma LDH level was significantly elevated (p < 0.05) following dietary treatment with AFB₁, while no significant difference was observed between the AF + BDP and CON treatments. Adding BDP to the AFB₁-contaminaed diet resulted in a significant reduction in AFM₁ concentration (483 vs. 665 ng L⁻¹) in the milk, AFM₁ excretion (9.14 vs. 12.71 μg d⁻¹), and transfer rate of dietary AFB₁ to milk AFM₁ (0.76 vs. 1.06%). In conclusion, the addition of BDP could be an alternative method for reducing the dietary AFB₁ bioavailability in dairy cows. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 3039 KiB

Open AccessEditor’s ChoiceArticle

Proanthocyanidins Alleviates AflatoxinB₁-Induced Oxidative Stress and Apoptosis through Mitochondrial Pathway in the Bursa of Fabricius of Broilers

by Shahid Ali Rajput, Cong Zhang, Yue Feng, Xiao Tian Wei, Mahmoud Mohamed Khalil, Imran Rashid Rajput, Dost Muhammad Baloch, Aftab Shaukat, Nasir Rajput, Hammad Qamar, Mubashar Hassan and Desheng Qi

Toxins 2019, 11(3), 157; https://doi.org/10.3390/toxins11030157 - 10 Mar 2019

Cited by 52 | Viewed by 4909

Abstract

Aflatoxin B₁ (AFB₁) is a serious threat to the poultry industry. Proanthocyanidins (PCs) demonstrates a broad range of biological, pharmacological, therapeutic, and chemoprotective properties. The aim of this study was to investigate the ameliorative effects of PCs against AFB₁ [...] Read more.

Aflatoxin B₁ (AFB₁) is a serious threat to the poultry industry. Proanthocyanidins (PCs) demonstrates a broad range of biological, pharmacological, therapeutic, and chemoprotective properties. The aim of this study was to investigate the ameliorative effects of PCs against AFB₁-induced histopathology, oxidative stress, and apoptosis via the mitochondrial pathway in the bursa of Fabricius (BF) of broilers. One hundred forty-four one-day old Cobb chicks were randomly assigned into four treatment groups of six replicates (6 birds each replicate) for 28 days. Groups were fed on the following four diets; (1) Basal diet without addition of PCs or AFB₁ (Control); (2) basal diet supplemented with 1 mg/kg AFB₁ from contaminated corn (AFB₁); (3) basal diet supplemented with 250 mg/kg PCs (PCs); and (4) basal diet supplemented with 1 mg/kg AFB₁ + 250 mg/kg PCs (AFB₁+ PCs). The present study results showed that antioxidant enzymes activities of total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST) in AFB₁ treated group were (p < 0.05) decreased, whereas malondialdehyde (MDA) contents were significantly increased in comparison with the control group. Furthermore, we found that dietary PCs treatment ameliorated AFB₁-induced oxidative stress in the BF through inhibiting the accumulation of MDA content and enhancing the antioxidant enzymes activities (T-SOD, CAT, GSH-Px, and GST). Similarly, PCs markedly enhanced messenger RNA (mRNA) expression of antioxidant genes (SOD, CAT, GPx1, and GST) in comparison with AFB₁ group. Moreover, histological results showed that PCs alleviated AFB₁-induced apoptotic cells in the BF of broilers. In addition, both mRNA and protein expression results manifested that mitochondrial-apoptosis-associated genes (Bax, caspase-9, caspase-3, and p53 and cytochrome c) showed up-regulation, while (Bcl-2) showed down-regulation in AFB₁ fed group. The supplementation of PCs to AFB₁ diet significantly reversed the mRNA and protein expression of these apoptosis-associated genes, as compared to the AFB₁ group. Our results demonstrated that PCs ameliorated AFB₁-induced oxidative stress by modulating the antioxidant defense system and apoptosis in the BF through mitochondrial pathway in broilers. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)

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14 pages, 1738 KiB

Open AccessEditor’s ChoiceArticle

Quercetin Inhibits the Proliferation and Aflatoxins Biosynthesis of Aspergillus flavus

by Xiu-Mei Li, Zhong-Yuan Li, Ya-Dong Wang, Jin-Quan Wang and Pei-Long Yang

Toxins 2019, 11(3), 154; https://doi.org/10.3390/toxins11030154 - 9 Mar 2019

Cited by 37 | Viewed by 4386

Abstract

In this work of quercetin’s anti-proliferation action on A. flavus, we revealed that quercetin can effectively hamper the proliferation of A. flavus in dose-effect and time-effect relationships. We tested whether quercetin induced apoptosis in A. flavus via various detection methods, such as [...] Read more.

In this work of quercetin’s anti-proliferation action on A. flavus, we revealed that quercetin can effectively hamper the proliferation of A. flavus in dose-effect and time-effect relationships. We tested whether quercetin induced apoptosis in A. flavus via various detection methods, such as phosphatidylserine externalization and Hoechst 33342 staining. The results showed that quercetin had no effect on phosphatidylserine externalization and cell nucleus in A. flavus. Simultaneously, quercetin reduced the levels of reactive oxygen species (ROS). For a better understanding of the molecular mechanism of the A. flavus response to quercetin, the RNA-Seq was used to explore the transcriptomic profiles of A. flavus. According to transcriptome sequencing data, quercetin inhibits the proliferation and aflatoxin biosynthesis by regulating the expression of development-related genes and aflatoxin production-related genes. These results will provide some theoretical basis for quercetin as an anti-mildew agent resource. Full article

(This article belongs to the Section Mycotoxins)

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29 pages, 20729 KiB

Open AccessEditor’s ChoiceArticle

Naja mossambica mossambica Cobra Cardiotoxin Targets Mitochondria to Disrupt Mitochondrial Membrane Structure and Function

by Boris Zhang, Feng Li, Zhengyao Chen, Indira H. Shrivastava, Edward S. Gasanoff and Ruben K. Dagda

Toxins 2019, 11(3), 152; https://doi.org/10.3390/toxins11030152 - 8 Mar 2019

Cited by 32 | Viewed by 5037

Abstract

Cobra venom cardiotoxins (CVCs) can translocate to mitochondria to promote apoptosis by eliciting mitochondrial dysfunction. However, the molecular mechanism(s) by which CVCs are selectively targeted to the mitochondrion to disrupt mitochondrial function remains to be elucidated. By studying cardiotoxin from Naja mossambica mossambica [...] Read more.

Cobra venom cardiotoxins (CVCs) can translocate to mitochondria to promote apoptosis by eliciting mitochondrial dysfunction. However, the molecular mechanism(s) by which CVCs are selectively targeted to the mitochondrion to disrupt mitochondrial function remains to be elucidated. By studying cardiotoxin from Naja mossambica mossambica cobra (cardiotoxin VII4), a basic three-fingered S-type cardiotoxin, we hypothesized that cardiotoxin VII4 binds to cardiolipin (CL) in mitochondria to alter mitochondrial structure/function and promote neurotoxicity. By performing confocal analysis, we observed that red-fluorescently tagged cardiotoxin rapidly translocates to mitochondria in mouse primary cortical neurons and in human SH-SY5Y neuroblastoma cells to promote aberrant mitochondrial fragmentation, a decline in oxidative phosphorylation, and decreased energy production. In addition, by employing electron paramagnetic resonance (EPR) and protein nuclear magnetic resonance (¹H-NMR) spectroscopy and phosphorescence quenching of erythrosine in model membranes, our compiled biophysical data show that cardiotoxin VII4 binds to anionic CL, but not to zwitterionic phosphatidylcholine (PC), to increase the permeability and formation of non-bilayer structures in CL-enriched membranes that biochemically mimic the outer and inner mitochondrial membranes. Finally, molecular dynamics simulations and in silico docking studies identified CL binding sites in cardiotoxin VII4 and revealed a molecular mechanism by which cardiotoxin VII4 interacts with CL and PC to bind and penetrate mitochondrial membranes. Full article

(This article belongs to the Special Issue Toxins-Membrane Interactions)

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19 pages, 3819 KiB

Open AccessEditor’s ChoiceArticle

Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action

by Indu Choudhary, Du Hyeon Hwang, Hyunkyoung Lee, Won Duk Yoon, Jinho Chae, Chang Hoon Han, Seungshic Yum, Changkeun Kang and Euikyung Kim

Toxins 2019, 11(3), 153; https://doi.org/10.3390/toxins11030153 - 8 Mar 2019

Cited by 26 | Viewed by 5937

Abstract

Nowadays, proliferation of jellyfish has become a severe matter in many coastal areas around the world. Jellyfish Nemopilema nomurai is one of the most perilous organisms and leads to significant deleterious outcomes such as harm to the fishery, damage the coastal equipment, and [...] Read more.

Nowadays, proliferation of jellyfish has become a severe matter in many coastal areas around the world. Jellyfish Nemopilema nomurai is one of the most perilous organisms and leads to significant deleterious outcomes such as harm to the fishery, damage the coastal equipment, and moreover, its envenomation can be hazardous to the victims. Till now, the components of Nemopilema nomurai venom (NnV) are unknown owing to scant transcriptomics and genomic data. In the current research, we have explored a proteomic approach to identify NnV components and their interrelation with pathological effects caused by the jellyfish sting. Altogether, 150 proteins were identified, comprising toxins and other distinct proteins that are substantial in nematocyst genesis and nematocyte growth by employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF/MS). The identified toxins are phospholipase A2, phospholipase D Li Sic Tox beta IDI, a serine protease, putative Kunitz-type serine protease inhibitor, disintegrin and metalloproteinase, hemolysin, leukotoxin, three finger toxin MALT0044C, allergens, venom prothrombin activator trocarin D, tripeptide Gsp 9.1, and along with other toxin proteins. These toxins are relatively well characterized in the venoms of other poisonous species to induce pathogenesis, hemolysis, inflammation, proteolysis, blood coagulation, cytolysis, hemorrhagic activity, and type 1 hypersensitivity, suggesting that these toxins in NnV can also cause similar deleterious consequences. Our proteomic works indicate that NnV protein profile represents valuable source which leads to better understanding the clinical features of the jellyfish stings. As one of the largest jellyfish in the world, Nemopilema nomurai sting is considered to be harmful to humans due to its potent toxicity. The identification and functional characterization of its venom components have been poorly described and are beyond our knowledge. Here is the first report demonstrating the methodical overview of NnV proteomics research, providing significant information to understand the mechanism of NnV envenomation. Our proteomics findings can provide a platform for novel protein discovery and development of practical ways to deal with jellyfish stings on human beings. Full article

(This article belongs to the Section Animal Venoms)

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12 pages, 1380 KiB

Open AccessEditor’s ChoiceArticle

Mycotoxins and Related Fungi in Italian Paddy Rice During the Growing Season and Storage

by Terenzio Bertuzzi, Marco Romani, Silvia Rastelli and Paola Giorni

Toxins 2019, 11(3), 151; https://doi.org/10.3390/toxins11030151 - 6 Mar 2019

Cited by 26 | Viewed by 4347

Abstract

Mycotoxigenic fungi and relative mycotoxins contamination were monitored in Italian paddy rice samples both in field during the growing season and the first five months of storage. Three experimental fields, nine rice varieties and three sowing densities were considered; then, different lots of [...] Read more.

Mycotoxigenic fungi and relative mycotoxins contamination were monitored in Italian paddy rice samples both in field during the growing season and the first five months of storage. Three experimental fields, nine rice varieties and three sowing densities were considered; then, different lots of paddy rice were stored in warehouses at different temperature regimes. Fusarium spp. and Aspergillus spp. were found to be the fungi most likely to produce mycotoxins throughout the growing season. In particular, A. flavus and A. niger were found only rarely both in field and in post-harvest, while A. versicolor was always present although in low concentrations. Penicillium spp. strains were isolated sporadically and were found to be irrelevant in Italian rice fungal contamination. Sterigmatocystin (STC) was the main mycotoxin found in Italian rice, while aflatoxin (AFB₁), deoxynivalenol (DON) and ochratoxin A (OTA) were rarely detected. Contamination generally increased from post-flowering to ripening; considering rice varieties, significant differences (p ≤ 0.01) were found in fungal contamination and STC production; no differences were observed between sowing densities. During storage, an increase in STC content was observed in higher temperature regimes, while all the other considered mycotoxins remained unchanged. These results indicated that contamination by STC, an emerging mycotoxin not legislatively regulated by the European Union, can be relevant in rice. Full article

(This article belongs to the Special Issue Mycotoxins and Cereal Quality)

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16 pages, 741 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Beneficial and Debilitating Effects of Environmental and Microbial Toxins, Drugs, Organic Solvents and Heavy Metals on the Onset and Progression of Multiple Sclerosis

by Mahmood Y. Hachim, Noha M. Elemam and Azzam A. Maghazachi

Toxins 2019, 11(3), 147; https://doi.org/10.3390/toxins11030147 - 5 Mar 2019

Cited by 20 | Viewed by 10085

Abstract

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system is common amongst young adults, leading to major personal and socioeconomic burdens. However, it is still considered complex and challenging to understand and treat, in spite of the efforts made to [...] Read more.

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system is common amongst young adults, leading to major personal and socioeconomic burdens. However, it is still considered complex and challenging to understand and treat, in spite of the efforts made to explain its etiopathology. Despite the discovery of many genetic and environmental factors that might be related to its etiology, no clear answer was found about the causes of the illness and neither about the detailed mechanism of these environmental triggers that make individuals susceptible to MS. In this review, we will attempt to explore the major contributors to MS autoimmunity including genetic, epigenetic and ecological factors with a particular focus on toxins, chemicals or drugs that may trigger, modify or prevent MS disease. Full article

(This article belongs to the Special Issue Toxins:10th Anniversary)

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14 pages, 2904 KiB

Open AccessEditor’s ChoiceArticle

Acute Kidney Injury Induced by Bothrops Venom: Insights into the Pathogenic Mechanisms

by Polianna Lemos Moura Moreira Albuquerque, Geraldo Bezerra da Silva Junior, Gdayllon Cavalcante Meneses, Alice Maria Costa Martins, Danya Bandeira Lima, Jacques Raubenheimer, Shihana Fathima, Nicholas Buckley and Elizabeth De Francesco Daher

Toxins 2019, 11(3), 148; https://doi.org/10.3390/toxins11030148 - 5 Mar 2019

Cited by 33 | Viewed by 5413

Abstract

Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood samples of patients after hospital [...] Read more.

Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood samples of patients after hospital admission resulting from Bothrops snakebite in a prospective cohort study in Northeast Brazil. Urinary and blood samples were evaluated during hospital stay in 63 consenting patients, divided into AKI and No-AKI groups according to the KDIGO criteria. The AKI group showed higher levels of urinary MCP-1 (Urinary monocyte chemotactic protein-1) (median 547.5 vs. 274.1 pg/mgCr; p = 0.02) and urinary NGAL (Neutrophil gelatinase-associated lipocalin) (median 21.28 vs. 12.73 ng/mgCr; p = 0.03). Risk factors for AKI included lower serum sodium and hemoglobin levels, proteinuria and aPTT (Activated Partial Thromboplastin Time) on admission and disclosed lower serum sodium (p = 0.01, OR = 0.73, 95% CI: 0.57–0.94) and aPTT (p = 0.031, OR = 26.27, 95% CI: 1.34–512.11) levels as independent factors associated with AKI. Proteinuria showed a positive correlation with uMCP-1 (r = 0.70, p < 0.0001) and uNGAL (r = 0.47, p = 0.001). FE_Na (Fractional Excretion of sodium) correlated with uMCP-1 (r = 0.47, P = 0.001) and uNGAL (r = 0.56, p < 0.0001). sCr (serum Creatinine) showed a better performance to predict AKI (AUC = 0.85) in comparison with new biomarkers. FE_K showed fair accuracy in predicting AKI (AUC = 0.92). Coagulation abnormality was strongly associated with Bothrops venom-related AKI. Urinary NGAL and MCP-1 were good biomarkers in predicting AKI; however, sCr remained the best biomarker. FE_K (Fractional Excretion of potassium) emerged as another diagnostic tool to predict early AKI. Positive correlations between uNGAL and uMCP-1 with proteinuria and FE_Na may signal glomerular and tubular injury. Defects in urinary concentrations highlighted asymptomatic abnormalities, which deserve further study. Full article

(This article belongs to the Section Animal Venoms)

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11 pages, 1395 KiB

Open AccessEditor’s ChoiceArticle

Preclinical Assessment of a New Polyvalent Antivenom (Inoserp Europe) against Several Species of the Subfamily Viperinae

by Alejandro García-Arredondo, Michel Martínez, Arlene Calderón, Asunción Saldívar and Raúl Soria

Toxins 2019, 11(3), 149; https://doi.org/10.3390/toxins11030149 - 5 Mar 2019

Cited by 18 | Viewed by 4548

Abstract

The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is [...] Read more.

The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is indicated for patients with systemic envenoming, of which there are approximately 4000 annual cases in Europe, and was suggested as an indication for young children and pregnant women, even if they do not have systemic symptoms. In the present study, the safety and venom-neutralizing efficacy of Inoserp Europe—a new F(ab’)₂ polyvalent antivenom, designed to treat envenoming by snakes in the Eurasian region—were evaluated. In accordance with World Health Organization recommendations, several quality control parameters were applied to evaluate the safety of this antivenom. The venom-neutralizing efficacy of the antivenom was evaluated in mice and the results showed it had appropriate neutralizing potency against the venoms of several species of Vipera, Montivipera, and Macrovipera. Paraspecificity of the antivenom was demonstrated as well, since it neutralized venoms of species not included in the immunization schemes and contains satisfactory levels of total proteins and F(ab’)₂ fragment concentration. Therefore, this new polyvalent antivenom could be effective in the treatment of snake envenoming in Europe, including Western Russia and Turkey. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 582 KiB

Open AccessEditor’s ChoiceArticle

Occurrence and Exposure Assessment of Aflatoxins and Deoxynivalenol in Cereal-Based Baby Foods for Infants

by Marta Herrera, Noemi Bervis, Juan José Carramiñana, Teresa Juan, Antonio Herrera, Agustín Ariño and Susana Lorán

Toxins 2019, 11(3), 150; https://doi.org/10.3390/toxins11030150 - 5 Mar 2019

Cited by 55 | Viewed by 6263

Abstract

Aflatoxins are carcinogenic to humans and deoxynivalenol causes digestive disorders, and both mycotoxins occur frequently in cereal-based foods. The purpose of this study was to investigate the occurrence and levels of aflatoxins (B1, B2, G1 and G2) and deoxynivalenol (DON) in cereal-based baby [...] Read more.

Aflatoxins are carcinogenic to humans and deoxynivalenol causes digestive disorders, and both mycotoxins occur frequently in cereal-based foods. The purpose of this study was to investigate the occurrence and levels of aflatoxins (B1, B2, G1 and G2) and deoxynivalenol (DON) in cereal-based baby foods as well as to calculate the estimated daily intakes (EDI) in different stages of infancy. Sixty samples of infant cereals (wheat-, corn-, rice-, oat-, and mixed grain-based) were collected during a 2-year period and analyzed by validated methods. Aflatoxins were detected in 12 samples (20%), six of which exceeded the EU maximum level for aflatoxin B1 set at 0.10 µg/kg. Deoxynivalenol appeared in 20% of baby food samples, with one sample exceeding the EU maximum level established at 200 µg/kg. There were no significant differences between gluten-free products for babies aged 4–6 months and multi-cereal products for infants aged 7–12 months, nor between whole-grain-based and refined ingredients. However, baby food products of organic origin showed significantly higher levels of deoxynivalenol than conventional ones (p < 0.05). It is proposed for the health protection of infants and young children, a vulnerable group, to establish the lowest maximum level for the sum of aflatoxins (B1, B2, G1 and G2) in baby food. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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13 pages, 2662 KiB

Open AccessEditor’s ChoiceArticle

Staphylococcal Enterotoxin C Is an Important Virulence Factor for Mastitis

by Rendong Fang, Jingchun Cui, Tengteng Cui, Haiyong Guo, Hisaya K. Ono, Chun-Ho Park, Masashi Okamura, Akio Nakane and Dong-Liang Hu

Toxins 2019, 11(3), 141; https://doi.org/10.3390/toxins11030141 - 2 Mar 2019

Cited by 30 | Viewed by 5486

Abstract

Staphylococcus aureus is an important bacterial pathogen causing bovine mastitis, but little is known about the virulence factor and the inflammatory responses in the mammary infection. Staphylococcal enterotoxin C (SEC) is the most frequent toxin produced by S. aureus, isolated from bovine [...] Read more.

Staphylococcus aureus is an important bacterial pathogen causing bovine mastitis, but little is known about the virulence factor and the inflammatory responses in the mammary infection. Staphylococcal enterotoxin C (SEC) is the most frequent toxin produced by S. aureus, isolated from bovine mastitis. To investigate the pathogenic activity of SEC in the inflammation of the mammary gland and the immune responses in an animal model, mouse mammary glands were injected with SEC, and the clinical signs, inflammatory cell infiltration, and proinflammatory cytokine production in the mammary glands were assessed. SEC induced significant inflammatory reactions in the mammary gland, in a dose-dependent manner. SEC-injected mammary glands showed a severe inflammation with inflammatory cell infiltration and tissue damage. In addition, interleukin (IL)-1β and IL-6 production in the SEC-injected mammary glands were significantly higher than those in the PBS control glands. Furthermore, the SEC-induced inflammation and tissue damage in the mammary gland were specifically inhibited by anti-SEC antibody. These results indicated, for the first time, that SEC can directly cause inflammation, proinflammatory cytokine production, and tissue damage in mammary glands, suggesting that SEC might play an important role in the development of mastitis associated with S. aureus infection. This finding offers an opportunity to develop novel treatment strategies for reduction of mammary tissue damage in mastitis. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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14 pages, 3190 KiB

Open AccessEditor’s ChoiceArticle

Molecular Interaction-Based Exploration of the Broad Spectrum Efficacy of a Bacillus thuringiensis Insecticidal Chimeric Protein, Cry1AcF

by Maniraj Rathinam, Karthik Kesiraju, Shweta Singh, Vinutha Thimmegowda, Vandna Rai, Debasis Pattanayak and Rohini Sreevathsa

Toxins 2019, 11(3), 143; https://doi.org/10.3390/toxins11030143 - 2 Mar 2019

Cited by 13 | Viewed by 4208

Abstract

Bacillus thuringiensis insecticidal proteins (Bt ICPs) are reliable and valuable options for pest management in crops. Protein engineering of Bt ICPs is a competitive alternative for resistance management in insects. The primary focus of the study was to reiterate the translational utility [...] Read more.

Bacillus thuringiensis insecticidal proteins (Bt ICPs) are reliable and valuable options for pest management in crops. Protein engineering of Bt ICPs is a competitive alternative for resistance management in insects. The primary focus of the study was to reiterate the translational utility of a protein-engineered chimeric Cry toxin, Cry1AcF, for its broad spectrum insecticidal efficacy using molecular modeling and docking studies. In-depth bioinformatic analysis was undertaken for structure prediction of the Cry toxin as the ligand and aminopeptidase1 receptors (APN1) from Helicoverpa armigera (HaAPN1) and Spodoptera litura (SlAPN1) as receptors, followed by interaction studies using protein-protein docking tools. The study revealed feasible interactions between the toxin and the two receptors through H-bonding and hydrophobic interactions. Further, molecular dynamics simulations substantiated the stability of the interactions, proving the broad spectrum efficacy of Cry1AcF in controlling H. armigera and S. litura. These findings justify the utility of protein-engineered toxins in pest management. Full article

(This article belongs to the Special Issue Insecticidal Toxins from Bacillus thuringiensis)

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15 pages, 2444 KiB

Open AccessEditor’s ChoiceArticle

Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host

by Lorena Tuchscherr, Christine Pöllath, Anke Siegmund, Stefanie Deinhardt-Emmer, Verena Hoerr, Carl-Magnus Svensson, Marc Thilo Figge, Stefan Monecke and Bettina Löffler

Toxins 2019, 11(3), 135; https://doi.org/10.3390/toxins11030135 - 1 Mar 2019

Cited by 36 | Viewed by 5769

Abstract

Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, [...] Read more.

Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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25 pages, 1497 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

by Johannes A. Eble

Toxins 2019, 11(3), 136; https://doi.org/10.3390/toxins11030136 - 1 Mar 2019

Cited by 46 | Viewed by 5904

Abstract

Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca²⁺- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share [...] Read more.

Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca²⁺- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share the robust C-type lectin domain (CTLD) fold but differ in a long loop, which either contributes to a sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. Most C-type lectin (-related) proteins assemble in ordered supramolecular complexes with a high versatility of subunit numbers and geometric arrays. Similarly versatile is their ability to inhibit or block their target molecules as well as to agonistically stimulate or antagonistically blunt a cellular reaction triggered by their target receptor. By utilizing distinct interaction sites differentially, SV-CLRPs target a plethora of molecules, such as distinct coagulation factors and receptors of platelets and endothelial cells that are involved in hemostasis, thrombus formation, inflammation and hematogenous metastasis. Because of their robust structure and their high affinity towards their clinically relevant targets, SV-CLRPs are and will potentially be valuable prototypes to develop new diagnostic and therapeutic tools in medicine, provided that the molecular mechanisms underlying their versatility are disclosed. Full article

(This article belongs to the Special Issue From Toxins to Drugs)

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13 pages, 3518 KiB

Open AccessEditor’s ChoiceArticle

Development of an Antifungal and Antimycotoxigenic Device Containing Allyl Isothiocyanate for Silo Fumigation

by Juan Manuel Quiles, Tiago de Melo Nazareth, Carlos Luz, Fernando Bittencourt Luciano, Jordi Mañes and Giuseppe Meca

Toxins 2019, 11(3), 137; https://doi.org/10.3390/toxins11030137 - 1 Mar 2019

Cited by 30 | Viewed by 4700

Abstract

The aims of this study were to evaluate the antifungal activity of the bioactive compound allyl isothiocyanate (AITC) against Aspergillus flavus (8111 ISPA) aflatoxins (AFs) producer and Penicillium verrucosum (D-01847 VTT) ochratoxin A (OTA) producer on corn, barley, and wheat. The experiments were [...] Read more.

The aims of this study were to evaluate the antifungal activity of the bioactive compound allyl isothiocyanate (AITC) against Aspergillus flavus (8111 ISPA) aflatoxins (AFs) producer and Penicillium verrucosum (D-01847 VTT) ochratoxin A (OTA) producer on corn, barley, and wheat. The experiments were carried out initially in a simulated silo system for laboratory scale composed of glass jars (1 L). Barley and wheat were contaminated with P. verrucosum and corn with A. flavus. The cereals were treated with a hydroxyethylcellulose gel disk to which 500 µL/L of AITC were added; the silo system was closed and incubated for 30 days at 21 °C. After that, simulated silos of 100 L capacity were used. Barley, wheat, and corn were contaminated under the same conditions as the previous trial and treated with disks with 5 mL of AITC, closed and incubated for 90 days at 21 °C. In both cases, the control test did not receive any antifungal treatment. The growth of the inoculated fungi and the reduction in the formation of AFs and OTA were determined. In the lab scale silo system, complete inhibition of fungal growth at 30 days has been observed. In corn, the reduction of aflatoxin B1 (AFB₁) was 98.5%. In the 100 L plastic drums, a significant reduction in the growth of A. flavus was observed, as well as the OTA formation in wheat (99.5%) and barley (92.0%). Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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15 pages, 759 KiB

Open AccessEditor’s ChoiceArticle

Effect of Wheat Milling Process on the Distribution of Alternaria Toxins

by Elizabet Janić Hajnal, Jasna Mastilović, Ferenc Bagi, Dejan Orčić, Dragana Budakov, Jovana Kos and Zagorka Savić

Toxins 2019, 11(3), 139; https://doi.org/10.3390/toxins11030139 - 1 Mar 2019

Cited by 26 | Viewed by 5141

Abstract

Alternaria toxins are mycotoxins produced by various Alternaria species which, besides the Fusarium species, represent the principal contaminants of wheat worldwide. As currently, only limited information on the behaviour of Alternaria toxins during processing of cereals is available, the objective of this study [...] Read more.

Alternaria toxins are mycotoxins produced by various Alternaria species which, besides the Fusarium species, represent the principal contaminants of wheat worldwide. As currently, only limited information on the behaviour of Alternaria toxins during processing of cereals is available, the objective of this study was to investigate the effect of the dry milling process of wheat on Alternaria toxins distribution. Alternariol (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TeA) content were analysed by high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in all milling fractions of untreated (control), fungicide-treated, Alternaria tenuissima inoculated and commercial wheat sample. After dry milling process, in last break and milling flows and by-products, increased concentration of examined Alternaria toxins was detected. TeA was quantified in almost all milling fractions in all tested wheat samples, while AOH and AME were detectable mostly in last break and milling flows and by-products. In respect to the contamination with Alternaria toxins, white flour can be considered as relatively safe product. Since Alternaria toxins are concentrated mainly in the peripheral parts of the kernel, a special attention should be given to their content in low-grade flours and milling by-products. Full article

(This article belongs to the Collection Understanding Mycotoxin Occurrence in Food and Feed Chains)

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22 pages, 22956 KiB

Open AccessEditor’s ChoiceArticle

Exploring Secondary Metabolite Profiles of Stachybotrys spp. by LC-MS/MS

by Annika Jagels, Viktoria Lindemann, Sebastian Ulrich, Christoph Gottschalk, Benedikt Cramer, Florian Hübner, Manfred Gareis and Hans-Ulrich Humpf

Toxins 2019, 11(3), 133; https://doi.org/10.3390/toxins11030133 - 27 Feb 2019

Cited by 24 | Viewed by 5124

Abstract

The genus Stachybotrys produces a broad diversity of secondary metabolites, including macrocyclic trichothecenes, atranones, and phenylspirodrimanes. Although the class of the phenylspirodrimanes is the major one and consists of a multitude of metabolites bearing various structural modifications, few investigations have been carried out. [...] Read more.

The genus Stachybotrys produces a broad diversity of secondary metabolites, including macrocyclic trichothecenes, atranones, and phenylspirodrimanes. Although the class of the phenylspirodrimanes is the major one and consists of a multitude of metabolites bearing various structural modifications, few investigations have been carried out. Thus, the presented study deals with the quantitative determination of several secondary metabolites produced by distinct Stachybotrys species for comparison of their metabolite profiles. For that purpose, 15 of the primarily produced secondary metabolites were isolated from fungal cultures and structurally characterized in order to be used as analytical standards for the development of an LC-MS/MS multimethod. The developed method was applied to the analysis of micro-scale extracts from 5 different Stachybotrys strains, which were cultured on different media. In that process, spontaneous dialdehyde/lactone isomerization was observed for some of the isolated secondary metabolites, and novel stachybotrychromenes were quantitatively investigated for the first time. The metabolite profiles of Stachybotrys species are considerably influenced by time of growth and substrate availability, as well as the individual biosynthetic potential of the respective species. Regarding the reported adverse effects associated with Stachybotrys growth in building environments, combinatory effects of the investigated secondary metabolites should be addressed and the role of the phenylspirodrimanes re-evaluated in future research. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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34 pages, 2097 KiB

Open AccessEditor’s ChoiceReview

The Role of Toxins in the Pursuit for Novel Analgesics

by Yossi Maatuf, Matan Geron and Avi Priel

Toxins 2019, 11(2), 131; https://doi.org/10.3390/toxins11020131 - 23 Feb 2019

Cited by 35 | Viewed by 6382

Abstract

Chronic pain is a major medical issue which reduces the quality of life of millions and inflicts a significant burden on health authorities worldwide. Currently, management of chronic pain includes first-line pharmacological therapies that are inadequately effective, as in just a portion of [...] Read more.

Chronic pain is a major medical issue which reduces the quality of life of millions and inflicts a significant burden on health authorities worldwide. Currently, management of chronic pain includes first-line pharmacological therapies that are inadequately effective, as in just a portion of patients pain relief is obtained. Furthermore, most analgesics in use produce severe or intolerable adverse effects that impose dose restrictions and reduce compliance. As the majority of analgesic agents act on the central nervous system (CNS), it is possible that blocking pain at its source by targeting nociceptors would prove more efficient with minimal CNS-related side effects. The development of such analgesics requires the identification of appropriate molecular targets and thorough understanding of their structural and functional features. To this end, plant and animal toxins can be employed as they affect ion channels with high potency and selectivity. Moreover, elucidation of the toxin-bound ion channel structure could generate pharmacophores for rational drug design while favorable safety and analgesic profiles could highlight toxins as leads or even as valuable therapeutic compounds themselves. Here, we discuss the use of plant and animal toxins in the characterization of peripherally expressed ion channels which are implicated in pain. Full article

(This article belongs to the Special Issue From Toxins to Drugs)

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21 pages, 5231 KiB

Open AccessEditor’s ChoiceArticle

Modulation of Mucin (MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A

by Xin Huang, Yanan Gao, Songli Li, Chenqing Wu, Jiaqi Wang and Nan Zheng

Toxins 2019, 11(2), 132; https://doi.org/10.3390/toxins11020132 - 23 Feb 2019

Cited by 37 | Viewed by 6639

Abstract

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which widely coexist in milk, may pose a serious threat to human health. Mucin is a major component of the intestinal mucus layer, which plays an important role in maintaining intestinal mucosal homeostasis. However, the effect [...] Read more.

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which widely coexist in milk, may pose a serious threat to human health. Mucin is a major component of the intestinal mucus layer, which plays an important role in maintaining intestinal mucosal homeostasis. However, the effect of mycotoxins AFM1 and OTA on intestinal mucin production is still not clear. This study aimed to investigate individual and interactive effects of mycotoxins AFM1 and OTA on the intestinal barrier and the mRNA expression of intestinal mucin (MUC2, MUC5AC and MUC5B) and on protein production in Caco-2/HT29-MTX cultures after 48 h of exposure. Our results show that individual mycotoxins and their mixtures significantly reduced intestinal cell viability and transepithelial electrical resistance (TEER) values, as well as significantly altered intestinal mucin mRNA expression and protein abundance. Moreover, OTA showed toxicity similar to AFM1 in cell viability and TEER value at the same concentration. When the two mycotoxins acted in combination, the synergistic effects observed in the assessment of cell viability and protein abundance in all mono- and co-cultures. In general, this study provides evidence that AFM1 and OTA can damage the intestine, and it contributes to optimized maximum permissible limits of mycotoxins in milk. Full article

(This article belongs to the Special Issue Modelling for Risk Assessment of Mycotoxins)

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13 pages, 10387 KiB

Open AccessEditor’s ChoiceArticle

Sphingomyelin Depletion from Plasma Membranes of Human Airway Epithelial Cells Completely Abrogates the Deleterious Actions of S. aureus Alpha-Toxin

by Sabine Ziesemer, Nils Möller, Andreas Nitsch, Christian Müller, Achim G. Beule and Jan-Peter Hildebrandt

Toxins 2019, 11(2), 126; https://doi.org/10.3390/toxins11020126 - 20 Feb 2019

Cited by 11 | Viewed by 4167

Abstract

Interaction of Staphylococcus aureus alpha-toxin (hemolysin A, Hla) with eukaryotic cell membranes is mediated by proteinaceous receptors and certain lipid domains in host cell plasma membranes. Hla is secreted as a 33 kDa monomer that forms heptameric transmembrane pores whose action compromises maintenance [...] Read more.

Interaction of Staphylococcus aureus alpha-toxin (hemolysin A, Hla) with eukaryotic cell membranes is mediated by proteinaceous receptors and certain lipid domains in host cell plasma membranes. Hla is secreted as a 33 kDa monomer that forms heptameric transmembrane pores whose action compromises maintenance of cell shape and epithelial tightness. It is not exactly known whether certain membrane lipid domains of host cells facilitate adhesion of Ha monomers, oligomerization, or pore formation. We used sphingomyelinase (hemolysin B, Hlb) expressed by some strains of staphylococci to pre-treat airway epithelial model cells in order to specifically decrease the sphingomyelin (SM) abundance in their plasma membranes. Such a pre-incubation exclusively removed SM from the plasma membrane lipid fraction. It abrogated the formation of heptamers and prevented the formation of functional transmembrane pores. Hla exposure of rHlb pre-treated cells did not result in increases in [Ca²⁺]_i, did not induce any microscopically visible changes in cell shape or formation of paracellular gaps, and did not induce hypo-phosphorylation of the actin depolymerizing factor cofilin as usual. Removal of sphingomyelin from the plasma membranes of human airway epithelial cells completely abrogates the deleterious actions of Staphylococcus aureus alpha-toxin. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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18 pages, 1720 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Mycotoxin Screening Tests in a Verification Study Involving First Time Users

by Veronica M. T. Lattanzio, Christoph von Holst, Vincenzo Lippolis, Annalisa De Girolamo, Antonio F. Logrieco, Hans G. J. Mol and Michelangelo Pascale

Toxins 2019, 11(2), 129; https://doi.org/10.3390/toxins11020129 - 20 Feb 2019

Cited by 26 | Viewed by 6408

Abstract

Rapid screening methods are currently recognized as a strategic tool for mycotoxin issues management. Specific guidelines for validation and verification of mycotoxin screening methods are set in the Commission Regulation (EU) No 2014/519. This regulation establishes that the “aim of the validation is [...] Read more.

Rapid screening methods are currently recognized as a strategic tool for mycotoxin issues management. Specific guidelines for validation and verification of mycotoxin screening methods are set in the Commission Regulation (EU) No 2014/519. This regulation establishes that the “aim of the validation is to demonstrate the fitness-for-purpose of the screening method” and focuses the entire validation procedure on determining specific cut-off values ensuring a maximum rate of false negative results of 5%. In addition, the assessment of the rate of false suspect results is addressed. With regard to rapid test-kits, ‘fitness-for-purpose’ includes not only the criteria more commonly considered when discussing laboratory-based methods (specificity, accuracy, and precision), but also more “practical” parameters such as speed and ease of implementation in a new operational environment. The latter means demonstrating under local conditions that performance parameters, as established during the validation, can be achieved by first time users. This goal can be achieved through “method verification”. The aim of the present study was to verify the fitness-for-purpose of mycotoxin screening methods when applied by first time users. This was achieved in one laboratory facility via results of a training course with multiple technicians attending. The verification study was organized similarly to a collaborative exercise and involved two groups comprising of 10 technicians each that used the methods for the first time. Different screening methods were applied for deoxynivalenol (DON) in wheat, which was mainly Enzyme Linked Immunosorbent Assay (ELISA), lateral flow device (LFD), fluorescence polarization immunoassay (FPIA), and liquid chromatography-high resolution mass spectrometry (LC-HRMS). An additional verification was done for aflatoxin B₁ (AFB₁) in maize and wheat using LFD and LC-HRMS, respectively. The results of analyses were used to calculate intermediate precision (RSD_ip, covering the inter-analyst variability in preparing the analytical samples and the precision under repeatability conditions) cut-off values and false suspect rates. RSD_ip ranged from 6.5% to 30% for DON, and from 16% to 33% for AFB₁. The highest obtained variances were associated with the AFB₁ analyses due to working with much lower mass fractions. The rate of false suspect results were lower than 0.1% for all tested methods. All methods showed a fit-for-purpose method performance profile, which allowed a clear distinction of samples containing the analytes at the screening target concentration (STC) from negative control samples. Moreover, the first time users obtained method performances similar to those obtained for validation studies previously performed on the screening methods included in the training course. Full article

(This article belongs to the Collection Biorecognition Assays for Mycotoxins)

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17 pages, 2093 KiB

Open AccessEditor’s ChoiceReview

Function and Role of ATP-Binding Cassette Transporters as Receptors for 3D-Cry Toxins

by Ryoichi Sato, Satomi Adegawa, Xiaoyi Li, Shiho Tanaka and Haruka Endo

Toxins 2019, 11(2), 124; https://doi.org/10.3390/toxins11020124 - 19 Feb 2019

Cited by 57 | Viewed by 6926

Abstract

When ABC transporter family C2 (ABCC2) and ABC transporter family B1 (ABCB1) were heterologously expressed in non-susceptible cultured cells, the cells swelled in response to Cry1A and Cry3 toxins, respectively. Consistent with the notion that 3D-Cry toxins form cation-permeable pores, Bombyx mori ABCC2 [...] Read more.

When ABC transporter family C2 (ABCC2) and ABC transporter family B1 (ABCB1) were heterologously expressed in non-susceptible cultured cells, the cells swelled in response to Cry1A and Cry3 toxins, respectively. Consistent with the notion that 3D-Cry toxins form cation-permeable pores, Bombyx mori ABCC2 (BmABCC2) facilitated cation-permeable pore formation by Cry1A when expressed in Xenopus oocytes. Furthermore, BmABCC2 had a high binding affinity (K_D) to Cry1Aa of 3.1 × 10⁻¹⁰ M. These findings suggest that ABC transporters, including ABCC2 and ABCB1, are functional receptors for 3D-Cry toxins. In addition, the Cry2 toxins most distant from Cry1A toxins on the phylogenetic tree used ABC transporter A2 as a receptor. These data suggest that 3D-Cry toxins use ABC transporters as receptors. In terms of inducing cell swelling, ABCC2 has greater activity than cadherin-like receptor. The pore opening of ABC transporters was hypothesized to be linked to their receptor function, but this was repudiated by experiments using mutants deficient in export activity. The synergistic relationship between ABCC2 and cadherin-like receptor explains their ability to cause resistance in one species of insect. Full article

(This article belongs to the Special Issue Insecticidal Toxins from Bacillus thuringiensis)

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12 pages, 735 KiB

Open AccessEditor’s ChoiceArticle

Personalized Bilateral Upper Limb Essential Tremor Therapy with Botulinum Toxin Using Kinematics

by Olivia Samotus, Jack Lee and Mandar Jog

Toxins 2019, 11(2), 125; https://doi.org/10.3390/toxins11020125 - 19 Feb 2019

Cited by 18 | Viewed by 4413

Abstract

Variability of multi-joint essential tremor (ET) between patients and within the two upper limbs makes a visual assessment for the determination of botulinum toxin type A (BoNT-A) injections challenging. Kinematic tremor analysis guidance has succeeded in overcoming this challenge by making effective long-term [...] Read more.

Variability of multi-joint essential tremor (ET) between patients and within the two upper limbs makes a visual assessment for the determination of botulinum toxin type A (BoNT-A) injections challenging. Kinematic tremor analysis guidance has succeeded in overcoming this challenge by making effective long-term unilateral BoNT-A injections for disabling ET. In this open-label study, 31 ET participants received three bilateral arm BoNT-A injection cycles over 30 weeks with follow-ups six-weeks post-treatment. Whole-arm kinematic assessment of tremor using a customized, automated algorithm provided muscle selection and dosing per muscle without clinician’s assessment. Efficacy endpoints included Fahn-Tolosa-Marin tremor scale, quality of life (QoL) questionnaire, and maximum grip strength. BoNT-A reduced tremor amplitude by 47.7% in both the arms at week-6 (p < 0.005) that persisted from weeks 18–30. QoL was improved by 26.5% (p < 0.005) over the treatment period. Functional interference due to tremor was reduced by 30% (p < 0.005) from weeks 6–30. Maximum grip strength was reduced at week 6 (p = 0.001) but was not functionally impaired for the participants. Effective bilateral ET therapy by personalized BoNT-A injections could be achieved using computer-assisted tremor analysis. By removing variability inherent within the clinical assessments, this standardized tremor analysis method enabled patients to have improved bimanual upper limb functionality after the first treatment. Full article

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20 pages, 1391 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Cellulosic Polymers and Curcumin to Reduce Aflatoxin B1 Toxic Effects on Performance, Biochemical, and Immunological Parameters of Broiler Chickens

by Bruno Solis-Cruz, Daniel Hernandez-Patlan, Victor M. Petrone, Karine P. Pontin, Juan D. Latorre, Eric Beyssac, Xochitl Hernandez-Velasco, Ruben Merino-Guzman, Casey Owens, Billy M. Hargis, Raquel Lopez-Arellano and Guillermo Tellez-Isaias

Toxins 2019, 11(2), 121; https://doi.org/10.3390/toxins11020121 - 16 Feb 2019

Cited by 40 | Viewed by 5745

Abstract

To evaluate the effect of cellulosic polymers (CEL) and curcumin (CUR) on aflatoxin B1 (AFB1) toxic effects on performance, and the biochemical and immunological parameters in broiler chickens, 150 one-day-old male broiler chicks were randomly allocated into five groups with three replicates of [...] Read more.

To evaluate the effect of cellulosic polymers (CEL) and curcumin (CUR) on aflatoxin B1 (AFB1) toxic effects on performance, and the biochemical and immunological parameters in broiler chickens, 150 one-day-old male broiler chicks were randomly allocated into five groups with three replicates of 10 chickens per pen: Negative Control (feed); AFB1 (feed + 2 ppm AFB1); CUR (feed + 2 ppm AFB1 + Curcumin 0.2%); CEL (feed + 2 ppm AFB1 + 0.3% Cellulosic polymers); and, CEL + CUR (feed + 2 ppm AFB1 + 0.3% Cellulose polymers + 0.2% Curcumin). Every week, body weight, body weight gain, feed intake, and feed conversion ratio were calculated. On day 21, liver, spleen, bursa of Fabricius, and intestine from five broilers per replicate per group were removed to obtain relative organ weight. Histopathological changes in liver, several biochemical biomarkers, antibody titers, and muscle and skin pigmentation were also recorded. Dietary addition of 0.3% CEL and 0.2% CUR separately significantly diminished some of the toxic effects resulting from AFB1 on performance parameters, relative organs weight, histopathology, immune response, and serum biochemical variables (P < 0.05); however, the combination of CUR and CEL showed a better-integrated approach for the management of poultry health problems that are related with the consumption of AFB1, since they have different mechanisms of action with different positive effects on the responses of broiler chickens. Full article

(This article belongs to the Special Issue Emerging Nanotechnology in Toxins Research)

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10 pages, 1286 KiB

Open AccessEditor’s ChoiceArticle

NaCl Inhibits Citrinin and Stimulates Monascus Pigments and Monacolin K Production

by Zhixin Zhen, Xiaoqian Xiong, Yingbao Liu, Jialan Zhang, Shaojin Wang, Li Li and Mengxiang Gao

Toxins 2019, 11(2), 118; https://doi.org/10.3390/toxins11020118 - 15 Feb 2019

Cited by 38 | Viewed by 5371

Abstract

Applications of beneficial secondary metabolites produced by Monascus purpureus (M. purpureus) could be greatly limited for citrinin, a kidney toxin. The link of NaCl with cell growth and secondary metabolites in M. purpureus was analyzed with supplementations of different concentrations of [...] Read more.

Applications of beneficial secondary metabolites produced by Monascus purpureus (M. purpureus) could be greatly limited for citrinin, a kidney toxin. The link of NaCl with cell growth and secondary metabolites in M. purpureus was analyzed with supplementations of different concentrations of NaCl in medium. The content of citrinin was reduced by 48.0% but the yellow, orange, red pigments and monacolin K productions were enhanced by 1.7, 1.4, 1.4 and 1.4 times, respectively, compared with those in the control using NaCl at 0.02 M at the 10th day of cultivation. NaCl didn’t affect the cell growth of M. purpureus. It was verified through the transcriptional down-regulation of citrinin synthesis genes (pksCT and ctnA) and up-regulation of the Monascus pigments (MPs) synthesis genes (pksPT and pigR). Moreover, the reactive oxygen species (ROS) levels were promoted by NaCl at the 2nd day of cultivation, and then inhibited remarkably with the extension of fermentation time. Meanwhile, the activities of superoxide dismutase (SOD) and catalase (CAT), and the contents of total glutathione (T-GSH) were significantly enhanced in the middle and late stages of cultivation. The inhibition effect on colony size and the growth of aerial mycelia was more obvious with an increased NaCl concentration. Acid and alkaline phosphatase (ACP and AKP) activities dramatically increased in NaCl treatments. NaCl could participate in secondary metabolites synthesis and cell growth in M. purpureus. Full article

(This article belongs to the Section Mycotoxins)

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36 pages, 3751 KiB

Open AccessEditor’s ChoiceReview

The Toxins of Nemertean Worms

by Ulf Göransson, Erik Jacobsson, Malin Strand and Håkan S. Andersson

Toxins 2019, 11(2), 120; https://doi.org/10.3390/toxins11020120 - 15 Feb 2019

Cited by 36 | Viewed by 16435

Abstract

Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate [...] Read more.

Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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12 pages, 2140 KiB

Open AccessEditor’s ChoiceCommunication

Distinctive Distribution of Secretory Phospholipases A₂ in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus)

by Choo Hock Tan, Kin Ying Wong, Nget Hong Tan, Tzu Shan Ng and Kae Yi Tan

Toxins 2019, 11(2), 116; https://doi.org/10.3390/toxins11020116 - 14 Feb 2019

Cited by 27 | Viewed by 5294

Abstract

The protein abundances of phospholipases A₂ in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A₂ (svPLA₂) in the cobras, the svPLA₂ activities for 15 cobra species were [...] Read more.

The protein abundances of phospholipases A₂ in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A₂ (svPLA₂) in the cobras, the svPLA₂ activities for 15 cobra species were examined with an acidimetric and a colorimetric assay, using egg yolk suspension and 4-nitro-3-octanoyloxy benzoic acid (NOBA) as the substrate. The colorimetric assay showed significant correlation between svPLA₂ enzymatic activities with the svPLA₂ protein abundances in venoms. High svPLA₂ activities were observed in the venoms of Asiatic spitting cobras (Naja sputatrix, Naja sumatrana) and moderate activities in Asiatic non-spitters (Naja naja, Naja atra, Naja kaouthia), African spitters (subgenus Afronaja), and forest cobra (subgenus Boulengerina). African non-spitting cobras of subgenus Uraeus (Naja haje, Naja annulifera, Naja nivea, Naja senegalensis) showed exceptionally low svPLA₂ enzymatic activities. The negligible PLA₂ activity in Uraeus cobra venoms implies that PLA₂ may not be ubiquitous in all snake venoms. The svPLA₂ in cobra envenoming varies depending on the cobra species. This may potentially influence the efficacy of cobra antivenom in specific use for venom neutralization. Full article

(This article belongs to the Section Animal Venoms)

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9 pages, 248 KiB

Open AccessEditor’s ChoiceOpinion

Biocontrol of Aspergillus and Fusarium Mycotoxins in Africa: Benefits and Limitations

by Victor Kagot, Sheila Okoth, Marthe De Boevre and Sarah De Saeger

Toxins 2019, 11(2), 109; https://doi.org/10.3390/toxins11020109 - 13 Feb 2019

Cited by 83 | Viewed by 8974

Abstract

Fungal contamination and the consequent mycotoxin production is a hindrance to food and feed safety, international trade and human and animal health. In Africa, fungal contamination by Fusarium and Aspergillus is heightened by tropical climatic conditions that create a suitable environment for pre- [...] Read more.

Fungal contamination and the consequent mycotoxin production is a hindrance to food and feed safety, international trade and human and animal health. In Africa, fungal contamination by Fusarium and Aspergillus is heightened by tropical climatic conditions that create a suitable environment for pre- and postharvest mycotoxin production. The biocontrol of Fusarium and its associated fusariotoxins has stagnated at laboratory and experimental levels with species of Trichoderma, Bacillus and atoxigenic Fusarium being tested as the most promising candidates. Hitherto, there is no impetus to upscale for field use owing to the inconsistent results of these agents. Non-aflatoxigenic strains of Aspergillus have been developed to create biocontrol formulations by outcompeting the aflatoxigenic strains, thus thwarting aflatoxins on the target produce by 70% to 90%. Questions have been raised on their ability to produce other mycotoxins like cyclopiazonic acid, to potentially exchange genetic material and to become aflatoxigenic with consequent deleterious effects on other organisms and environments. Other biocontrol approaches to mitigate aflatoxins include the use of lactic acid bacteria and yeast species which have demonstrated the ability to prevent the growth of Aspergillus flavus and consequent toxin production under laboratory conditions. Nevertheless, these strategies seem to be ineffective under field conditions. The efficacy of biological agents is normally dependent on environmental factors, formulations’ safety to non-target hosts and the ecological impact. Biocontrol agents can only be effectively evaluated after long-term use, causing a never-ending debate on the use of live organisms as a remedy to pests and diseases over the use of chemicals. Biocontrol should be used in conjunction with good agricultural practices coupled with good postharvest management to significantly reduce mycotoxins in the African continent. Full article

(This article belongs to the Special Issue Biological Control and Post-Harvest Detoxification of Mycotoxins as Strategies to Reduce the Impact of Mycotoxins)

9 pages, 452 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin Contamination of Milk Marketed in Pakistan: A Longitudinal Study

by Agha Waqar Yunus, Nida Imtiaz, Haider Khan, Mohammed Nawaz Mohammed Ibrahim and Yusuf Zafar

Toxins 2019, 11(2), 110; https://doi.org/10.3390/toxins11020110 - 13 Feb 2019

Cited by 27 | Viewed by 5293

Abstract

A longitudinal one-year study was conducted to determine aflatoxin M₁ levels in different types of milk marketed in Pakistan. Processed and raw liquid milk from 21 sources, two milk powder and six tea whitener brands were sampled on monthly basis from Islamabad. [...] Read more.

A longitudinal one-year study was conducted to determine aflatoxin M₁ levels in different types of milk marketed in Pakistan. Processed and raw liquid milk from 21 sources, two milk powder and six tea whitener brands were sampled on monthly basis from Islamabad. The aflatoxin M₁ levels in liquid milk were lower (p < 0.05) in summer (April to July) compared with the levels in winter (January, November and December). The mean aflatoxin M₁ levels were 254.9, 939.5, and 1535.0 ng/L in UHT, pasteurized, and raw milk, respectively (differing at p < 0.001). The mean toxin level in powdered milk after reconstitution was 522.1 ng/L. Overall, 12.9, 41.0, 91.9 and 50.0% of the UHT, pasteurized, raw and powdered milk samples, respectively, exceeded the Codex maximum tolerable limit of 500 ng of aflatoxin M₁/L. It was estimated that consumers of raw and processed milk were exposed to 11.9 and 4.5 ng aflatoxin M₁, respectively, per kg of body weight daily. The study indicates potential aflatoxin M₁ exposure risks for the consumers of raw milk in the country. The levels of the toxin though comparatively lower in milk powder, requires attention as this type of milk is consumed by infants. Full article

(This article belongs to the Special Issue Food Safety and Natural Toxins)

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15 pages, 3479 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Probiotic Supplementation on Performance and the Histopathological Changes in Liver and Kidneys in Broiler Chickens Fed Diets with Aflatoxin B₁

by Katarzyna Śliżewska, Bożena Cukrowska, Stefania Smulikowska and Joanna Cielecka-Kuszyk

Toxins 2019, 11(2), 112; https://doi.org/10.3390/toxins11020112 - 13 Feb 2019

Cited by 76 | Viewed by 8925

Abstract

The aim of the study was to investigate the toxic effects of aflatoxin B₁ (AFB₁) and efficacy of a probiotic preparation containing L. reuteri, L. plantarum, L. pentosus, L. rhamnosus and L. paracasei and Saccharomyces cerevisiae yeasts [...] Read more.

The aim of the study was to investigate the toxic effects of aflatoxin B₁ (AFB₁) and efficacy of a probiotic preparation containing L. reuteri, L. plantarum, L. pentosus, L. rhamnosus and L. paracasei and Saccharomyces cerevisiae yeasts to ameliorate their effects in broiler chickens. A total of 168 one-day-old female Ross 308 broilers were randomly allocated to six groups. Three wheat and soybean meal-based diets were prepared: Control diet and diets contaminated with 1 or 5 mg/kg AFB₁ supplied in moldy wheat. All diets were unsupplemented or supplemented with probiotic, cold pelleted and fed from 1 to 35 day of life. Feeding diet with 1 mg AFB₁/kg did not affect performance, but a diet with 5 mg AFB₁ resulted in a significant reduction of feed intake and BWG, both diets induced liver and kidneys enlargement. The probiotic supplementation of the diets partially ameliorated those negative effects and resulted in a significant increase of AFB₁ excretion. It was accompanied by the reduced level of AFB₁ residues in the liver from 8.9 to 3.7 and from 11.8 to 5.9 µg/kg, in kidneys from 7.9 to 2.5 and from 13.7 to 4.1 µg/kg in birds fed the less and more contaminated diets, respectively. AFB₁ exposure caused many severe histopathological changes in the liver and kidneys of broilers, probiotic supplementation significantly reduced the changes of these organs. It may be concluded that the probiotic supplementation can be used to alleviate the negative effects of contamination of broiler feed with AFB₁ on bird health and product security. Full article

(This article belongs to the Section Mycotoxins)

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29 pages, 2493 KiB

Open AccessEditor’s ChoiceReview

Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors

by Matthew W. Turner, Leanna A. Marquart, Paul D. Phillips and Owen M. McDougal

Toxins 2019, 11(2), 113; https://doi.org/10.3390/toxins11020113 - 13 Feb 2019

Cited by 24 | Viewed by 5871

Abstract

Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of marine snails of genus Conus. α-CTxs are potent [...] Read more.

Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of marine snails of genus Conus. α-CTxs are potent and selective antagonists for a variety of nAChR isoforms. Over the past 40 years, α-CTxs have proven to be valuable molecular probes capable of differentiating between closely related nAChR subtypes and have contributed greatly to understanding the physiological role of nAChRs in the mammalian nervous system. Here, we review the amino acid composition and structure of several α-CTxs that selectively target nAChR isoforms and explore strategies and outcomes for introducing mutations in native α-CTxs to direct selectivity and enhance binding affinity for specific nAChRs. This review will focus on structure-activity relationship studies involving native α-CTxs that have been rationally mutated and molecular interactions that underlie binding between ligand and nAChR isoform. Full article

(This article belongs to the Special Issue Marine Toxins Affecting Neuronal Function)

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12 pages, 1010 KiB

Open AccessEditor’s ChoiceReview

Developmental Toxicity of Mycotoxin Fumonisin B₁ in Animal Embryogenesis: An Overview

by Chompunut Lumsangkul, Hsin-I Chiang, Neng-Wen Lo, Yang-Kwang Fan and Jyh-Cherng Ju

Toxins 2019, 11(2), 114; https://doi.org/10.3390/toxins11020114 - 13 Feb 2019

Cited by 56 | Viewed by 5802

Abstract

A teratogenic agent or teratogen can disturb the development of an embryo or a fetus. Fumonisin B₁ (FB₁), produced by Fusarium verticillioides and F. proliferatum, is among the most commonly seen mycotoxins and contaminants from stale maize and other [...] Read more.

A teratogenic agent or teratogen can disturb the development of an embryo or a fetus. Fumonisin B₁ (FB₁), produced by Fusarium verticillioides and F. proliferatum, is among the most commonly seen mycotoxins and contaminants from stale maize and other farm products. It may cause physical or functional defects in embryos or fetuses, if the pregnant animal is exposed to mycotoxin FB₁. Due to its high similarity in chemical structure with lipid sphinganine (Sa) and sphingosine (So), the primary component of sphingolipids, FB₁ plays a role in competitively inhibiting Sa and So, which are key enzymes in de novo ceramide synthase in the sphingolipid biosynthetic pathway. Therefore, it causes growth retardation and developmental abnormalities to the embryos of hamsters, rats, mice, and chickens. Moreover, maternal FB₁ toxicity can be passed onto the embryo or fetus, leading to mortality. FB₁ also disrupts folate metabolism via the high-affinity folate transporter that can then result in folate insufficiency. The deficiencies are closely linked to incidences of neural tube defects (NTDs) in mice or humans. The purpose of this review is to understand the toxicity and mechanisms of mycotoxin FB₁ on the development of embryos or fetuses. Full article

(This article belongs to the Section Mycotoxins)

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12 pages, 1999 KiB

Open AccessEditor’s ChoiceArticle

Inhibition of Aflatoxin Production by Paraquat and External Superoxide Dismutase in Aspergillus flavus

by Tomohiro Furukawa and Shohei Sakuda

Toxins 2019, 11(2), 107; https://doi.org/10.3390/toxins11020107 - 12 Feb 2019

Cited by 23 | Viewed by 3864

Abstract

Aflatoxin contamination of crops is a worldwide problem, and elucidation of the regulatory mechanism of aflatoxin production, for example relative to the oxidative–antioxidative system, is needed. Studies have shown that oxidative stress induced by reactive oxygen species promotes aflatoxin production. However, superoxide has [...] Read more.

Aflatoxin contamination of crops is a worldwide problem, and elucidation of the regulatory mechanism of aflatoxin production, for example relative to the oxidative–antioxidative system, is needed. Studies have shown that oxidative stress induced by reactive oxygen species promotes aflatoxin production. However, superoxide has been suggested to have the opposite effect. Here, we investigated the effects of the superoxide generator, paraquat, and externally added superoxide dismutase (SOD) on aflatoxin production in Aspergillus flavus. Paraquat with an IC₅₀ value of 54.9 µM inhibited aflatoxin production without affecting fungal growth. It increased cytosolic and mitochondrial superoxide levels and downregulated the transcription of aflatoxin biosynthetic cluster genes, including aflR, a key regulatory protein. The addition of bovine Cu/ZnSOD to the culture medium suppressed the paraquat-induced increase in superoxide levels, but it did not fully restore paraquat-inhibited aflatoxin production because bovine Cu/ZnSOD with an IC₅₀ value of 17.9 µg/mL itself inhibited aflatoxin production. Externally added bovine Cu/ZnSOD increased the SOD activity in fungal cell extracts and upregulated the transcription of genes encoding Cu/ZnSOD and alcohol dehydrogenase. These results suggest that intracellular accumulation of superoxide impairs aflatoxin production by downregulating aflR expression, and that externally added Cu/ZnSOD also suppresses aflatoxin production by a mechanism other than canonical superoxide elimination activity. Full article

(This article belongs to the Collection Aflatoxins)

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21 pages, 2614 KiB

Open AccessEditor’s ChoiceArticle

Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom

by Paula A. L. Calabria, Lhiri Hanna A. L. Shimokawa-Falcão, Monica Colombini, Ana M. Moura-da-Silva, Katia C. Barbaro, Eliana L. Faquim-Mauro and Geraldo S. Magalhaes

Toxins 2019, 11(2), 108; https://doi.org/10.3390/toxins11020108 - 12 Feb 2019

Cited by 16 | Viewed by 5559

Abstract

Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be [...] Read more.

Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant Loxosceles toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from Loxosceles gaucho. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by L. gaucho, L. laeta, and L. intermedia venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against Loxosceles ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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21 pages, 6463 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland Transcriptomics

by Ho Phin Chong, Kae Yi Tan, Nget Hong Tan and Choo Hock Tan

Toxins 2019, 11(2), 104; https://doi.org/10.3390/toxins11020104 - 11 Feb 2019

Cited by 28 | Viewed by 6483

Abstract

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja [...] Read more.

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja sputatrix were reported previously through cloning studies. To investigate this species venom genes’ diversity, de novo venom-gland transcriptomics of N. sumatrana from West Malaysia was conducted using next-generation sequencing technology. Genes encoding toxins represented only 60 of the 55,396 transcripts, but were highly expressed, contributing to 79.22% of total gene expression (by total FPKM) in the venom-glands. The toxin transcripts belong to 21 families, and 29 transcripts were further identified as full-length. Three-finger toxins (3FTx) composed of long, short, and non-conventional groups, constituted the majority of toxin transcripts (91.11% of total toxin FPKM), followed by phospholipase A₂ (PLA₂, 7.42%)—which are putatively pro-inflammatory and cytotoxic. The remaining transcripts in the 19 families were expressed at extremely low levels. Presumably, these toxins were associated with ancillary functions. Our findings unveil the diverse toxin genes unique to N. sumatrana, and provide insights into the pathophysiology of N. sumatrana envenoming. Full article

(This article belongs to the Section Animal Venoms)

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9 pages, 2727 KiB

Open AccessEditor’s ChoiceArticle

Photocatalytic Degradation of Deoxynivalenol over Dendritic-Like α-Fe₂O₃ under Visible Light Irradiation

by Huiting Wang, Jin Mao, Zhaowei Zhang, Qi Zhang, Liangxiao Zhang, Wen Zhang and Peiwu Li

Toxins 2019, 11(2), 105; https://doi.org/10.3390/toxins11020105 - 11 Feb 2019

Cited by 51 | Viewed by 5127

Abstract

Deoxynivalenol (DON) is a secondary metabolite produced by Fusarium, which is a trichothecene mycotoxin. As the main mycotoxin with high toxicity, wheat, barley, corn and their products are susceptible to contamination of DON. Due to the stability of this mycotoxin, traditional methods [...] Read more.

Deoxynivalenol (DON) is a secondary metabolite produced by Fusarium, which is a trichothecene mycotoxin. As the main mycotoxin with high toxicity, wheat, barley, corn and their products are susceptible to contamination of DON. Due to the stability of this mycotoxin, traditional methods for DON reduction often require a strong oxidant, high temperature and high pressure with more energy consumption. Therefore, exploring green, efficient and environmentally friendly ways to degrade or reduce DON is a meaningful and challenging issue. Herein, a dendritic-like α-Fe₂O₃ was successfully prepared using a facile hydrothermal synthesis method at 160 °C, which was systematically characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). It was found that dendritic-like α-Fe₂O₃ showed superior activity for the photocatalytic degradation of DON in aqueous solution under visible light irradiation (λ > 420 nm) and 90.3% DON (initial concentration of 4.0 μg/mL) could be reduced in 2 h. Most of all, the main possible intermediate products were proposed through high performance liquid chromatography-mass spectrometry (HPLC-MS) after the photocatalytic treatment. This work not only provides a green and promising way to mitigate mycotoxin contamination but also may present useful information for future studies. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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